Platelet adhesion to VLDL, LDL, HDL, and to a mixture of purified apolipoproteins was examined. Platelets adhered to all the classes of lipoproteins tested. VLDL and the apolipoprotein mixture promoted the greatest degree of adhesion. Platelet adhesion was inhibited by addition of EDTA, RGD-containing peptides and anti-GPIIb-IIIa, monoclonal antibodies. Platelets from patients with Glanzmann's Thrombasthenia which lack the GPIIb-IIIa receptor adhered to VLDL less than half as well as did normal platelets. These results demonstrate that the major circulating lipoproteins can mediate in vitro platelet adhesion and that this adhesion occurs via platelet integrin receptors. We postulate that lipoprotein mediated platelet adhesion may play an important role in the progression of atherosclerosis.